Prolonged neoadjuvant treatment in locally advanced tumours: A novel concept based on biological considerations

Background: Neoadjuvant chemotherapy is increasingly applied in patients wi th locally advanced cancers of many tumour types. Usually three cycles of c hemotherapy are administered to reduce the tumour size prior to local thera py, and another three cycles thereafter. The chemotherapy certainly contrib utes to the improved outcome of this approach. However, biological factors within the primary tumour have been neglected, while they might also contri bute to the eradication of micrometastases. We believe that the neoadjuvant strategy can be improved by optimally exploiting certain biological factor s inherent to the primary tumour. In a group of patients with locally advan ced breast cancer (LABC) we studied this concept. Recently we described the clinical results of this phase II study in patients with LABC treated with neoadjuvant chemotherapy plus granulocyte-macrophage colony-stimulating fa ctor (GM-CSF). A remarkable good response and survival was seen. In contras t to other studies we applied six cycles of neoadjuvant treatment in stead of a sandwich approach consisting of three cycles before and three cycles a fter local therapy, leaving the primary tumour and draining lymph nodes in situ for a prolonged period. In addition, GM-CSF was administered as a haem atopoietic growth factor in stead of granulocyte colony-stimulating factor (G-CSF) as GM-CSF has also immune-stimulating properties. Our findings defi nitely warrant further exploration of prolonged neoadjuvant systemic treatm ent in combination with GM-CSF in other high risk primary tumours. Hypotheses. The promising results of our study may be attributable to two p otential biological phenomena. Firstly, the conservation of the tumour and its draining lymph nodes may prove to be an essential part of this approach , with particular emphasis on the activation of tumour specific cytotoxic T cells. Secondly, circulating angiogenesis inhibitors originating from the primary tumour may enhance the effect of chemotherapy on micrometastases.